High Serum Alkaline Phosphatase Activity Research Articles

Effects of Dietary Phosphorus Deficiency and High Phosphorus Content on the Growth Performance, Serum Variables, and Tibia Development in Goslings

Understanding how dietary phosphorus (P) regulates the growth and skeletal development of goslings is essential for fully utilizing P in the production of geese. We aimed to study the effects of dietary P deficiency and high P content on growth performance, serum variables, tibia quality, and mRNA expression of osteogenesis-related genes in tibia to reveal how dietary P regulates bone development in goslings. Two hundred and sixteen one-day-old Jiangnan White male geese were fed corn-soybean meal diets for 14 days. The diets were set with the same calcium (Ca) level (0.80%) and three non-phytate P (NPP) levels: 0.08% (P deficiency), 0.38% (P control), and 0.80% (P high content). Each treatment consisted of six replicates with 12 goslings in each replicate. The P deficient group had a high cumulative mortality of 26.67% with lower body weight (BW), average daily feed intake (ADFI), average daily gain (ADG), serum P contents, tibia width, tibia length, tibia fresh weight at d 14 as compared with the control and high P content group (p ≤ 0.05). Dietary P deficiency caused a reduction in the goslings’ tibia strength, tibia ash content, tibia Ca content, and tibia P content during d 4–d 14 (p < 0.05). The P deficiency reduced tibia mRNA expression of osteoprotegerin (OPG) and runt-related transcription factor 2 (Runx2) on d 7 (p < 0.05), whereas up-regulated serum alkaline phosphatase (ALP) activity, calcitonin (CT) content, and the tibia mRNA ratio of receptor activator of NF-κB ligand (RNAKL)/OPG during d 7–d 14 (p < 0.05). The serum 1,25-(OH2)D3 content, serum bone Gla-protein (BGP), and the mRNA relative expression of RNAKL and BGP in tibia were decreased in the NPP 0.08% and 0.80% groups compared with the control on d 14 (p < 0.05). In conclusion, dietary P deficiency induced acute rickets in goslings as early as the fourth day. A P deficiency hindered the tibia and body growth partly due to poor skeletal calcification caused by a down-expression of osteogenesis-related genes regulated by high serum ALP activity and calcitonin contents and lower serum BGP and skeletal P contents.

Randomized, placebo-controlled, 28-day safety and pharmacokinetics evaluation of repeated oral cannabidiol administration in healthy dogs.

To determine the safety and pharmacokinetics of various doses of plant-derived cannabidiol (CBD) versus placebo following repeated oral administration. 20 healthy adult Beagles. In a randomized, blinded, placebo-controlled trial, dogs were randomized to 5 groups balanced in body weight and sex (n = 4 dogs/group) and received a CBD (1, 2, 4, or 12 mg/kg; from cannabis extract) or placebo oil formulation PO once daily for 28 days. Outcome variables were assessed through daily health observations, veterinary examinations, CBC, and serum biochemical analysis. Blood samples were collected at various time points to estimate 24-hour pharmacokinetic profiles of CBD and selected metabolites (7-carboxy-CBD and 7-hydroxy-CBD). Repeated CBD administration was well tolerated by dogs, with no clinically important changes in measured safety outcomes. Veterinary examinations revealed no clinically important abnormal findings. Adverse events were mild in severity. Relative to placebo administration, CBD administration at 12 mg/kg/d resulted in more gastrointestinal adverse events (mainly hypersalivation) and significantly higher serum alkaline phosphatase activity. Total systemic exposure to CBD increased on a dose-dependent basis following both acute (first dose) and chronic (28 days) administration. Within each CBD dose group, repeated administration increased total systemic exposure to CBD 1.6- to 3.3-fold. The 24-hour trough plasma CBD concentrations were also dose dependent, with a steady state reached following 2 weeks of administration. Repeated, daily oral administration of the CBD formulation led to dose-dependent increases in total systemic exposure to CBD and 24-hour trough plasma concentrations in healthy dogs. These findings could help guide dose selection.

Fat powder can be a feasible lipid source in aquafeed for the carnivorous marine teleost golden pompano, Trachinotus ovatus

In the production of aquafeeds, exogenous liquid oils are usually added directly or by vacuum coating. In order to evaluate the practicality of fat powder in aquafeeds and aquaculture, four isoproteic (46%) and isolipidic (12%) diets named FOl, BOl, FOp, and BOp were prepared with fish oil (FO) or blend oil (BO, consisting of fish, soybean, rapeseed, and perilla oils) or their corresponding fat powder as dietary lipid, respectively. Each diet was fed to triplicate groups of golden pompano Trachinotus ovatus juveniles (initial body weight about 15.10 g) in floating sea cages (1.0 × 1.0 × 2.0 m, 30 fish per cage) for 10 weeks. Fish were fed to nearly satiation at two times each day. The results showed that the final weight, weight gain rate (WGR), specific growth rate (SGR), food conversion ratio (FCR), condition factor (CF), viscerosomatic index (VSI), and survival rate (SUR) displayed no significant difference among the four dietary groups (P > 0.05), while the hepatosomatic index (HSI) in the BOp group (1.01) was significantly lower than that in FO-base groups (1.19–1.23) (P < 0.05). The fatty acid (FA) composition in livers or dorsal muscle showed no difference between the fish fed the diets from liquid oil and corresponding fat powder. A significantly high serum alkaline phosphatase (ALP) activity and low hepatic malondialdehyde (MDA) level were detected in the BOp group (P < 0.05). Moreover, the mRNA levels of hepatic glutathione peroxidase (gsh-px), superoxide dismutase (sod), and catalase (cat), as well as intestinal FA binding protein 2 (fabp2) and FA transport protein 4 (fatp4) genes in one or both of the fat powder groups, were significantly higher than those in the corresponding liquid oil groups (P < 0.05). Additionally, the peroxide value (POV) and MDA level in FOp and BOp diets were less than 27% of those in FOl and BOl diets after stored at − 20 °C for 3 months. These results demonstrated that fat powder diets, especially BOp, displayed better effects than liquid oil diets in lipid oxidation stability, liver health, and FA transportation in T. ovatus, which indicated that fat powder can be a feasible lipid source in aquafeed. To our knowledge, this is the first report on the practical application of fat powder in aquaculture, which may provide a new form of lipid addition in the aquafeeds industry.

Higher serum alkaline phosphatase activity in infants born to vitamin D-deficient mothers.

Low maternal serum 25-hydroxy vitamin D (25(OH)D) level during pregnancy contributes to vitamin D deficiency in infants at birth, which is associated with multiple potential adverse effects on fetal skeletal mineralization and growth. We studied the relationship between maternal 25(OH)D level and newborn serum alkaline phosphatase activity (ALP) at term. In this prospective cross-sectional hospital-based study, venous blood samples of healthy pregnant mothers were drawn to measure 25(OH)D levels within 6 h of delivery. Cord blood samples were examined for calcium, phosphorus levels, and ALP activity immediately after birth. In addition, we also recorded the newborns' anthropometric measurements. Seventy-two percent (n = 108/150) of mothers in our study were vitamin D-deficient (serum 25(OH)2D < 25 nmol/l). In a multivariate logistic regression model, young maternal age (odds ratio (OR) = 0.94, 95% CI 0.88-0.99, p = 0.04) and increased weight (OR = 1.03, 95% CI 1.01-1.07, p = 0.02) as well as decreased milk intake (OR = 0.31, 95% CI 0.13-0.74, p = 0.009) were all significantly associated with maternal vitamin D deficiency. ALP activity was significantly higher in newborns of vitamin D-deficient compared with vitamin D-non-deficient mothers (median = 176 (IQR = 139-221) and 156 (IQR = 132-182), respectively, p = 0.04). A significant inverse correlation (Pearson's coefficient = - 0.18, p = 0.03) was observed between maternal 25(OH)D levels and babies' ALP activities. This association persisted in a multivariate logistic regression model (OR = 3.46, 95% CI 1.18-10.18, p = 0.024). Our findings indicate that newborns of vitamin D-deficient mothers have higher serum ALP activity than those of non-deficient mothers, which might be related to increased bone turnover rather than just being a marker for bone formation. This could have a potential negative impact on fetal bone development and subsequent skeletal growth.

Serum biochemical profile of neonatal buffalo calves

ABSTRACT Serum blood samples from 50 Murrah buffalo calves were examined in this study. The animals were allocated into three groups according to the number of parturitions of their mothers: G1 (n= 15) calves from primiparous buffaloes, G2 (n= 19) calves from buffaloes with two to four parturitions, and G3 (n= 16) calves from buffaloes with five or more parturitions. Blood samples were taken at birth, before colostrum ingestion, at 24h, 48h, and 72h after birth, and at 7, 14, 21, and 30 days after birth for determination of levels of gammaglutamyl transferase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), creatine kinase, total protein, albumin, globulins (including immunoglobulin G), iron, total calcium, ionized calcium, phosphorus, sodium, and potassium. The age of the calves was found to influence all of the biochemical parameters, with the exception of ionized calcium and potassium in the calves in groups G1 and G3. The calving order was found to influence AST, GGT, total protein, albumin, and globulins, including IgG. The high serum ALP activity in the first two days after birth indicates that measurement of the levels of this enzyme may be used as an indirect method of assessing passive immunity transfer.

Effects of short-term anti-inflammatory glucocorticoid treatment on clinicopathologic, echocardiographic, and hemodynamic variables in systemically healthy dogs.

OBJECTIVE To investigate mechanisms by which anti-inflammatory doses of orally administered intermediate-acting glucocorticoids (prednisone) could predispose dogs to progression of heart disease or congestive heart failure. ANIMALS 11 client-owned dogs with allergic dermatitis and 11 matched healthy control dogs. PROCEDURES Clinicopathologic, echocardiographic, and hemodynamic variables were measured. Dogs with allergic dermatitis then received prednisone (1 mg/kg, PO) once daily for 14 consecutive days beginning on day 0 (baseline), followed by a tapering and washout period; control dogs received no treatment. Measurements were repeated on days 7, 14, and 35. Linear mixed modeling was used to compare changes in variables across measurement points and between dog groups. RESULTS Prednisone administration caused no significant changes in serum sodium or potassium concentration, blood glucose concentration, or target echocardiographic variables. The change from baseline in systolic arterial blood pressure at day 7 was significantly greater in prednisone-treated dogs than in control dogs. Expected changes in hematologic and serum biochemical values with prednisone administration (neutrophilia, eosinopenia, isosthenuria, and high serum alkaline phosphatase and alanine aminotransferase activities) also occurred in the prednisone-treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that anti-inflammatory doses of orally administered glucocorticoids have the potential to adversely impact cardiac function in dogs by causing an increase in blood pressure and thus increased cardiac afterload.

Clinical signs, treatment, and prognostic factors for dogs with histoplasmosis.

OBJECTIVE To determine the clinical manifestations of histoplasmosis in a large sample of dogs, compare outcomes achieved with fluconazole versus itraconazole, and identify variables available at the time of diagnosis with prognostic value. DESIGN Retrospective case series with nested cohort study. ANIMALS 79 dogs with confirmed histoplasmosis evaluated at 2 veterinary teaching hospitals from 1999 through 2015. PROCEDURES Medical records were reviewed and data extracted regarding clinical signs at evaluation, physical examination findings, clinical laboratory values, other diagnostic test results, treatments, and outcomes. Data were compared between antifungal agents used (fluconazole or itraconazole) and between other variables. RESULTS Various breeds were represented. Working and herding breeds had mostly disseminated histoplasmosis, and toy breeds had mostly the gastrointestinal form. The diagnosis was often achieved with noninvasive techniques, such as cytologic evaluation of rectal scrape samples (n = 24) or blood films (15). Clinical remission was achieved in 16 of 25 (64%) dogs receiving fluconazole and 17 of 24 (71%) dogs receiving itraconazole. No differences were identified between antifungal agents in survival, clinical remission, or disease relapse rates. Identified negative prognostic factors included Great Pyrenees breed, dyspnea, need for oxygen supplementation, icterus, palpable abdominal organomegaly, anemia, thrombocytopenia, hypercalcemia, high serum alkaline phosphatase activity, and hyperbilirubinemia, whereas diarrhea was a positive prognostic factor. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that histoplasmosis should be considered in a sick dog of any breed in an endemic area. Clinical signs may be nonspecific. Diagnosis may often be possible with noninvasive and inexpensive tests. Either fluconazole or itraconazole may be an effective treatment option.

Zinc supplementation reduces RANKL/OPG ratio and prevents bone architecture alterations in ovariectomized and type 1 diabetic rats

Type 1 diabetes mellitus (T1DM) and estrogen deficiency are associated with several alterations in bone turnover. Zinc (Zn) is required for growth, development, and overall health. Zinc has been used in complementary therapy against bone loss in several diseases. We hypothesized that Zn supplementation represents a potential therapy against severe bone loss induced by the combined effect of estrogen deficiency and T1DM. We evaluated the protective effect of Zn against bone alterations in a chronic model of these disorders. Female Wistar rats were ramdomized into 3 groups (5 rats each): control, OVX/T1DM (ovariectomized rats with streptozotocin-induced T1DM), and OVX/T1DM+Zn (OVX/T1DM plus daily Zn supplementation). Serum biochemical, bone histomorphometric, and molecular analyses were performed. Histomorphometric parameters were similar between the control and OVX/T1DM+Zn groups, suggesting that Zn prevents bone architecture alterations. In contrast, the OVX/T1DM group showed significantly lower trabecular width and bone area as well as greater trabecular separation than the control. The OVX/T1DM and OVX/T1DM+Zn groups had significantly higher serum alkaline phosphatase activity than the control. The supplemented group had higher levels of serum-ionized calcium and phosphorus than the nonsupplemented group. The RANKL/OPG ratio was similar between the control and OVX/T1DM+Zn groups, whereas it was higher in the OVX/T1DM group. In conclusion, Zn supplementation prevents bone alteration in chronic OVX/T1DM rats, as demonstrated by the reduced RANKL/OPG ratio and preservation of bone architecture. The findings may represent a novel therapeutic approach to preventing OVX/T1DM-induced bone alterations.

Analysis of serum corticosteroid-induced alkaline phosphatase isoenzyme in dogs with hepatobiliary diseases.

To reveal the relationship between canine corticosteroid-induced alkaline phosphatase isoenzyme activity and hepatobiliary diseases. Retrospective analysis of the relationship between serum corticosteroid-induced alkaline phosphatase activity and diagnosis, serum cortisol concentration and alanine transferase activity in dogs with hepatobiliary diseases. Dogs with a history of glucocorticoid administration were excluded. Seventy-two dogs with hepatobiliary diseases were analysed. The serum corticosteroid-induced alkaline phosphatase concentration was increased in dogs with hepatobiliary diseases. There was no correlation between serum cortisol concentration and serum corticosteroid-induced alkaline phosphatase percentage or activity. Dogs with hepatobiliary disease can exhibit high serum alkaline phosphatase activity even if the dogs have not been administrated glucocorticoids and the serum cortisol concentration is normal.

DIAGNOSTIC ASPECTS OF PAGET’S DISEASE OF BONE IN CLINICAL PRACTICE

Paget’s disease of bone (PDB) is a chronic localized skeletal disease that belongs to a group of metabolic osteopathies and is characterized by impaired bone remodeling to form foci of increased bone resorption followed by replacement with an excessive amount of defective, less durable bone that is prone to deformities and pathologic fractures. The course of PDB shows three stages: rarefaction, compaction, and coarse-trabecular remodeling – each of which is characterized by certain clinical, biochemical, and radiological manifestations. The majority of the clinical manifestations of the disease are associated with skeletal injury. The disease is characterized by the appearance of bone and joint pain in case of secondary osteoarthritis, bone deformities, pathological fractures, hearing loss due to damage to the skull bones, etc. In many patients, the disease is asymptomatic and detected incidentally after finding a high serum alkaline phosphatase activity or during bone X-ray for any pathological processes, but it can be diagnosed fairly late in the development of complications, as shown in the clinical examples. A combination of clinical, biochemical, morphological data and radiological findings allows for a diagnosis. The use of bisphosphonates is the method of choice for the treatment of PDB.

Elevated liver enzymes

Elevated liver enzymes are a frequent finding in both symptomatic and asymptomatic patients necessitating further evaluation to clarify the underlying disease. Three different patterns of increased liver enzymes can be defined to allow for a more precise and rational further diagnostic approach. A predominant increase in transaminase activities reflects a disturbance of hepatocellular integrity which can be found in patients with viral hepatitis, genetic liver diseases like Wilson`s disease or hemochromatosis, and drug-induced liver diseases. A second pattern is characterized by high serum alkaline phosphatase and γ-glutamyltranspeptidase activities indicating cholestatic liver diseases. The next important diagnostic measure in this group is an ultrasound study discerning intra- from extrahepatic cholestasis. Intrahepatic cholestatic diseases include primary and secondary sclerosing cholangitis, genetic disturbances of canalicular membrane transporters or drug-induced liver dieseases. Extrahepatic cholestasis involves obstruction of the large bile ducts by gall stones or tumors. The third enzym pattern is defined by a predominant rise in γ-glutamyl transpeptidase which is observed in alcoholic or non-alcoholic fatty liver disease and infiltrating liver diseases. A rise in liver enzymes is not necessarily indicative of a primary hepatic origin. Extrahepatic diseases often cause similarly increased serum activities. In addition even higher values can be observed under normal conditions during pregnancy or in adolescens. Lower values in asymptomatic patients should only be controlled since more than 30% of elevated transaminases spontaneously normalize during follow-up.

Hematological and Serum Biochemical Abnormalities Associated with a Suspected Case of Genital Squamous Cell Carcinoma in a Gray Nigerian Mare

An 18-year-old gray mare (a crossbred Nigerian horse) was observed to have a proliferative tissue growth with multiple necrotic areas, which was suspected to be a genital squamous cell carcinoma. The mucous membrane of the eyes and gingiva of the mare were pale, and the animal was dull and insensitive, had an abnormal posture and gait, with conspicuous protruding proliferative tissue mass around the vagina and vulva. Blood samples for hematology analysis and serum biochemistry were collected from the jugular vein and determinations followed standard procedures. Hematological examination revealed that the mare had macrocytic anaemia, leukocytosis, neutrophilia, monocytosis, higher than normal erythrocyte sedimentation rate. Serum biochemical assays showed that serum activities of aspartate aminotransferase and alanine aminotransferase were slightly lower than normal. High serum alkaline phosphatase activity was recorded, with high serum total protein level that was mainly due to high serum globulin level. The mare also had a lower than normal total cholesterol. High serum creatinine level was observed. These hematological and serum biochemical findings are commonly associated with genital squamous cell carcinomas in animals and humans.

Pituitary-dependent hyperadrenocorticism in a terrier dog: A case report

We report a case of pituitary-dependent hyperadrenocorticism in a 10-year-old, female, terrier dog. The animal was admitted due to polyphagia, weight gain, polyuria, polydipsia, hair loss, exercise intolerance and panting at rest. On physical examination, abdominal distention, truncal and bilaterally symmetric alopecia, thin hypotonic skin, comedones, bruising, hyperpigmentation and calcinosis cutis on the dorsal midline were observed. Hematologic investigations showed stress leukogram, high serum alkaline phosphatase activity, mild to moderate alanine aminotransferase activity, hypercholesterolemia, hypertriglyceridemia and hyperglycemia. Mild generalized interstitial lung patterns and hepatomegaly were detected in the radiographs. Bilaterally symmetric normal-sized adrenal glands were also diagnosed in ultrasonography. Diagnosis of pituitary-dependent hyperadrenocorticism was confirmed with low-dose dexamethasone suppression test. The dog was successfully treated with mitotane.

Hepatocutaneous syndrome in Shih Tzus: 31 cases (1996-2014).

To characterize findings in Shih Tzus with progressive superficial necrolytic dermatitis and degenerative vacuolar hepatopathy consistent with hepatocutaneous syndrome. Retrospective case series. 31 Shih Tzus. Medical records were reviewed to obtain information on signalment, history, treatment, outcome, and results of clinicopathologic testing, abdominal ultrasonography, and histologic examination of skin and liver specimens. A pedigree analysis was performed. There were 16 males and 15 females. Median age at the time of diagnosis was 8 years (range, 5 to 14 years). Common clinical signs included lethargy, inappetence, weight loss, and lameness. Twenty-five dogs had cutaneous lesions consistent with hepatocutaneous syndrome; the remaining 6 initially only had hepatic abnormalities, but 3 of the 6 subsequently developed cutaneous lesions. Common clinicopathologic abnormalities included microcytosis (15/24 [63%] dogs) and high serum alkaline phosphatase activity (24/24 [100%] dogs). Hepatic ultrasonographic findings included a hyperechoic or heteroechoic appearance to the parenchyma with innumerable hypoechoic nodules. Histologic hepatic lesions consisted of degenerative vacuolar (glycogen and lipid) hepatopathy associated with minimally fibrotic to nonfibrotic, noninflammatory, proliferative nodules. Pedigree analysis confirmed a common ancestry in 12 of 18 dogs. Median survival time was 3 months (range, 1 to 36 months). Results suggested that HCS may have a heritable component in Shih Tzus, although the condition may also be identified in Shih Tzus without affected relatives. Clinical, clinicopathologic, ultrasonographic, and histologic abnormalities in affected Shih Tzus were similar to those previously reported for dogs of other breeds with HCS.

Association of alkaline phosphatase with isolated coronary artery ectasia

Background. It has been shown that alkaline phosphatase (ALP) is a reliable marker for cardiovascular events and mortality. However, there is no data available regarding the association of ALP with isolated coronary artery ectasia (CAE). The aim of the present study was to assess the serum ALP activity in isolated CAE. Methods. Seventy-nine patients with isolated CAE (59 males; mean age, 52 ± 12 years) and 88 age- and gender-matched normal subjects (73 males; mean age, 52 ± 7 years) were enrolled. Baseline characteristics were recorded in both groups and serum ALP activity were compared between the two groups. Results. Patients with angiography-proved isolated CAE had significantly higher serum ALP activity compared with angiographic normal controls (72.41 ± 29.97 vs. 59.27 ± 14.46, p < 0.001). In the multivariate analysis, increased ALP (OR = 1.037, 95% CI 1.017–1.057, p < 0.001) were independent predictors for the presence of isolated CAE. A cut-off of ≥ 66.5 U/L of ALP activity measured on admission had a 60.8% sensitivity and 75.0% specificity in predicting isolated CAE by receiver operating characteristic (ROC) curve analysis. Conclusion. Our data firstly demonstrated that serum ALP activity, a readily available clinical laboratory value, was associated with the presence of isolated CAE.

Haematological and biochemical reference intervals of four feline breeds

Many feline breeds have been generated from a small number of ancestors. Thus, breed-specific peculiarities can be expected, which could include haematological and biochemical measurements. Despite this, there are only a few reports on breed-specific reference intervals (RI). This information is essential in routine practice where results from individual patients are usually compared with an RI. The aim was to compare haematological and biochemical data from clinically healthy Abyssinian, Holy Birman, Norwegian Forest and Siberian cats with published RIs to assess whether the published RIs are acceptable in these breeds. Comparison with established RIs using guidelines from the National Committee for Clinical Laboratory Standards and the American Society of Veterinary Clinical Pathology, revealed a number of breed-related clinicopathological differences. New RIs were established, but in most cases the new RIs overlapped with published RIs, and the use of the breed-specific data would minimally affect the clinical interpretation of laboratory results. Important differences that could result in misinterpretation of laboratory results were as follows: microcytosis and high α2-globulin concentrations in Abyssinian cats; high serum creatinine, α2-globulin and glucose concentrations in Holy Birman cats; high serum alkaline phosphatase activity and calcium and phosphate concentration in Norwegian Forest cats; low β2-globulin and γ-globulin concentrations in Norwegian Forest and Siberian cats. Breed-specific RIs should be used for these analytes. In addition, care should be taken in interpreting clinicopathological data in purebred cats for which specific RIs have not been established.

Safety Assessment of Poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334, 335, 338, 401, 402, 403, and 407, Poloxamer 105 Benzoate, and Poloxamer 182 Dibenzoate as Used in Cosmetics

Poloxamers are polyoxyethlyene, polyoxypropylene block polymers. The impurities of commercial grade Poloxamer 188, as an example, include low-molecular-weight substances (aldehydes and both formic and acetic acids), as well as 1,4-dioxane and residual ethylene oxide and propylene oxide. Most Poloxamers function in cosmetics as surfactants, emulsifying agents, cleansing agents, and/or solubilizing agents, and are used in 141 cosmetic products at concentrations from 0.005% to 20%. Poloxamers injected intravenously in animals are rapidly excreted in the urine, with some accumulation in lung, liver, brain, and kidney tissue. In humans, the plasma concentration of Poloxamer 188 (given intravenously) reached a maximum at 1 h, then reached a steady state. Poloxamers generally were ineffective in wound healing, but were effective in reducing postsurgical adhesions in several test systems. Poloxamers can cause hypercholesterolemia and hypertriglyceridemia in animals, but overall, they are relatively nontoxic to animals, with LD(50) values reported from 5 to 34.6 g/kg. Short-term intravenous doses up to 4 g/kg of Poloxamer 108 produced no change in body weights, but did result in diffuse hepatocellular vacuolization, renal tubular dilation in kidneys, and dose-dependent vacuolization of epithelial cells in the proximal convoluted tubules. A short-term inhalation toxicity study of Poloxamer 101 at 97 mg/m(3) identified slight alveolitis after 2 weeks of exposure, which subsided in the 2-week postexposure observation period. A short-term dermal toxicity study of Poloxamer 184 in rabbits at doses up to 1000 mg/kg produced slight erythema and slight intradermal inflammatory response on histological examination, but no dose-dependent body weight, hematology, blood chemistry, or organ weight changes. A 6-month feeding study in rats and dogs of Poloxamer 188 at exposures up to 5% in the diet produced no adverse effects. Likewise, Poloxamer 331 (tested up to 0.5 g/kg day(-1)), Poloxamer 235 (tested up to 1.0 g/kg day(-1)), and Poloxamer 338 (at 0.2 or 1.0 g/kg day(-1)) produced no adverse effects in dogs. Poloxamer 338 (at 5.0 g/kg day(-1)) produced slight transient diarrhea in dogs. Poloxamer 188 at levels up to 7.5% in diet given to rats in a 2-year feeding study produced diarrhea at 5% and 7.5% levels, a small decrease in growth at the 7.5% level, but no change in survival. Doses up to 0.5 mg/kg day(-1) for 2 years using rats produced yellow discoloration of the serum, high serum alkaline phosphatase activity, and elevated serum glutamicpyruvic transaminase and glutamic-oxalacetic transaminase activities. Poloxamers are minimal ocular irritants, but are not dermal irritants or sensitizers in animals. Data on reproductive and developmental toxicity of Poloxamers were not found. An Ames test did not identify any mutagenic activity of Poloxamer 407, with or without metabolic activation. Several studies have suggested anticarcinogenic effects of Poloxamers. Poloxamers appear to increase the sensitivity to anticancer drugs of multidrug-resistant cancer cells. In clinical testing, Poloxamer 188 increased the hydration of feces when used in combination with a bulk laxative treatment. Compared to controls, one study of angioplasty patients receiving Poloxamer 188 found a reduced myocardial infarct size and a reduced incidence of reinfarction, with no evidence of toxicity, but two other studies found no effect. Poloxamer 188 given to patients suffering from sickle cell disease had decreased pain and decreased hospitilization, compared to controls. Clinical tests of dermal irritation and sensitization were uniformly negative. The Cosmetic Ingredient Review (CIR) Expert Panel stressed that the cosmetic industry should continue to use the necessary purification procedures to keep the levels below established limits for ethylene oxide, propylene oxide, and 1,4-dioxane. The Panel did note the absence of reproductive and developmental toxicity data, but, based on molecular weight and solubility, there should be little skin penetration and any penetration of the skin should be slow. Also, the available data demonstrate that Poloxamers that are introduced into the body via routes other than dermal exposure have a rapid clearance from the body, suggesting that there would be no risk of reproductive and/or developmental toxicity. Overall, the available data do not suggest any concern about carcinogenesis. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used, and at what concentration, indicates a pattern of use. Based on these safety test data and the information that the manufacturing process can be controlled to limit unwanted impurities, the Panel concluded that these Poloxamers are safe as used.

Serum liver enzyme activities in healthy Miniature Schnauzers with and without hypertriglyceridemia

To determine whether hypertriglyceridemia in healthy Miniature Schnauzers is associated with high serum liver enzyme activities. Cross-sectional study. 65 Miniature Schnauzers with serum triglyceride concentrations within the reference range (group 1), 20 Miniature Schnauzers with slightly high serum triglyceride concentrations (group 2), and 20 Miniature Schnauzers with moderately to severely high serum triglyceride concentrations (group 3). Questionnaires regarding each dog's medical history were completed, and serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and G-glutamyltransferase (GGT) activities were measured. Median serum ALP activity was significantly higher in group 3 than in group 1 or 2 dogs, but was not significantly higher in group 2 than in group 1 dogs. Median serum ALT activity was significantly higher in group 3 than in group 1 dogs, but was not significantly different between any of the other groups. Compared with group 1 dogs, group 2 and 3 dogs were significantly more likely to have high serum ALP activity (odds ratio, 26.2 and 192.6, respectively). Group 3 dogs also were significantly more likely to have high serum ALT activity (odds ratio, 8.0), serum AST activity (odds ratio, 3.7), and serum GGT activity (odds ratio, 11.3), compared with group 1 dogs. Group 3 dogs were significantly more likely (odds ratio, 31.0) to have > or = 2 high serum liver enzyme activities than were group 1 dogs. Results suggested that moderate to severe hypertriglyceridemia was associated with high serum liver enzyme activities in Miniature Schnauzers.

Vacuolar hepatopathy in dogs: 336 cases (1993–2005)

To determine disorders associated with vacuolar hepatopathy (VH), morphologic hepatic and clinicopathologic abnormalities, and affiliation with steroidogenic hormone excess in dogs. Retrospective case series. Animals-336 dogs with histologically confirmed moderate or severe VH. Information on signalment, results of diagnostic testing, definitive diagnoses, and exposure to glucocorticoids (ie, exogenous glucocorticoid administration or high endogenous concentrations of steroidogenic hormones) was obtained from medical records. Dogs were grouped by underlying disorder, glucocorticoid exposure, acinar zonal distribution of lesions, and histologic severity. 12 disease groups (neoplastic, acquired hepatobiliary, neurologic, immune-mediated, gastrointestinal tract, renal, infectious, cardiac disease, diabetes mellitus, portosystemic vascular anomaly, adrenal gland dysfunction, and miscellaneous disorders) were identified. There were 186 (55%) dogs with and 150 (45%) dogs without evidence of glucocorticoid exposure. Acinar zonal distribution of hepatic vacuolation and clinicopathologic values did not differ between dogs with and without evidence of glucocorticoid exposure. However, a 3-fold increased likelihood of severe VH was associated with steroidogenic hormone exposure. Of 226 dogs with high serum alkaline phosphatase activity, 102 (45%) had no evidence of glucocorticoid exposure. Results suggest that neoplasia and congenital or acquired hepatobiliary disease are common in dogs with VH and provide support for the suggestion that VH, high alkaline phosphatase activity, and illness-invoked physiologic stress may be associated. Histologic confirmation of VH should initiate a diagnostic search for a primary disease if glucocorticoid treatment and hyperadrenocorticism are ruled out.

Serum alkaline phosphatase activity in Scottish Terriers versus dogs of other breeds

To determine whether Scottish Terriers have higher serum alkaline phosphatase (ALP) activities and a higher prevalence of diseases commonly associated with high serum ALP activity than do dogs of other breeds. Retrospective case-control study. 85 Scottish Terriers and 340 age-matched control dogs that were not Scottish Terriers. Medical records were reviewed, and data for year of evaluation, age, sex, breed, serum ALP activity, and final diagnosis were recorded. Scottish Terriers had a significantly higher mean serum ALP activity than did control dogs (1,520 U/L vs 306 U/L). Regardless of breed, dogs that had a disease commonly associated with high serum ALP activity had a significantly higher mean serum ALP activity than did dogs without such diseases (1,304 U/L vs 427 U/L). Scottish Terriers were 2.4 times as likely to have a disease commonly associated with high serum ALP activity than were control dogs, but Scottish Terriers with diseases commonly associated with high serum ALP activity had a significantly higher mean ALP activity than did control dogs with such diseases (2,073 U/L vs 909 U/L), and Scottish Terriers without such diseases had a significantly higher mean serum ALP activity than did control dogs without such diseases (1,349 U/L vs 228 U/L). Results suggest that Scottish Terriers have higher serum ALP activities than do dogs of other breeds. Although Scottish Terriers also have a higher prevalence of diseases associated with high serum ALP activity, this alone did not explain the higher mean serum ALP activity in the breed.